Contract Development and Manufacturing Organizations (CDMOs) in the pharmaceutical/biotech industry rely heavily on state-of-the-art instrumentation to bring their client’s products from drug development through drug manufacturing to the patient. An analytical chemist will use advanced, computer-controlled analytical instrumentation to measure the safety and quality of these products, perform process and product development studies, and ensure their company complies with regulatory requirements.
To better serve their client’s needs as technology and the pharmaceutical industry advances, a CDMO must know when to acquire new and emerging technologies, increase their overall instrument capacity, and continually maintain their existing validated instrumentation.
A pharmaceutical company may rely on a CDMO to do all of the analytical testing for an active pharmaceutical ingredient, or a finished drug product, for which the CDMO is doing the formulation, manufacturing, filling, packaging, storage, and fulfillment. The CDMO’s goal is to ensure that the client’s drug is pure, potent, and stable over its projected shelf life.
Technology is advancing quickly. Just as with an iPhone or the latest car model, analytical instrument manufacturers are constantly innovating, and working hard to generate demand for the latest and greatest chemical/biological assays or instrument detectors. A specific project or client may provide the CDMO with the incentive to buy equipment or consumables uniquely needed for the project, especially if they have a demand that is currently outside of the CDMO’s capabilities. Working with the CDMO to expand services or equipment may be a more appealing option versus having another outsourced partner.
A large pharmaceutical company may have 300 high performance liquid chromatography (HPLC) units in place. (In my former capacity as a R&D scientist at Eli Lilly & Company, I had three of my own.) That level of redundancy is unrealistic for a smaller-scale CDMO. An HPLC unit will cost $100,000-$250,000, depending on its capabilities. It is common practice for a CDMO to expect the client to provide at least some of the equipment for a large-scale project.
Assessment of Instrumentation
The first requirement of a CDMO is to regularly assess its analytical instrumentation needs based on current and future products, client-driven decisions to increase capacity, and other factors. To help with this assessment we track instrumentation hours, dollars spent on maintenance, and our general efficiency. We assess our testing backlog and the likelihood that increasing our instrument capacity will enable us to take on more or expanded projects. These assessments drive scheduling and budget decisions in evaluating and purchasing new analytical instrumentation and software.
The software may be supplied by the instrumentation vendor, or more advanced software from a third-party. Singota has several UHPLC/HPLC instruments, but in particular one remaining HPLC system has been in service for 15 years! It continues to provide outstanding results efficiently because the company has regularly updated the analytics software to process the HPLC data, generate reports, create automated workflows, and enforce GMP standards. These vendor supported upgrades have enabled Singota to keep a reliable instrument in service while evolving processes to keep up with industry standards.
Occasionally, when onboarding a client project, a CDMO will recognize that the product requires a test for which the CDMO does not have the necessary instruments. This is increasingly likely for the newer protein drugs and biologics/biosimilars coming out of client’s pipelines. Once a new instrument need is identified, the procurement process begins. Here, a bench scientist has what may be a counterintuitive advantage in working at a small, agile CDMO as opposed to a larger organization — the purchase decision can be made by one or two officers, more quickly than with a procurement process that must filter up through several layers of authority, often up to board level. Up-front planning/budgeting, a good relationship with your equipment vendor, and sound justification can bring in the new instrument in a matter of weeks.
Validation of Equipment
Every purchase of new instrumentation starts with installation on site at the CDMO, typically in collaboration with the vendor. Then the equipment must be set up with defined processes and documented in Standard Operating Procedure (SOP) format. The IT department is involved in setting up networking, software, and security. The quality assurance team is engaged to ensure alignment of the process with the standards set by both internal requirements and outside regulatory bodies.
Once the CDMO’s internal stakeholders are satisfied with the performance and documentation, members of the clients’ staff may come on-site to do their own audits. The equipment, standards, and processes all are subject to FDA audits as well, roughly every two to three years. However other agencies (State Board of Pharmacy, DEA, etc.) are also eligible, and welcome, to visit the CDMO and audit unannounced when appropriate.
Analytical instruments are sensitive and need to be recalibrated minimally at pre-determined intervals. The CDMO should be doing daily checks on all validated equipment and every 6 to 12 months more in-depth performance should be checked against the original vendor specifications.
The CDMO’s client is looking not just for accurate data, but for consistently accurate data over long periods of time. If purity or stability data on a compound varies significantly over time, that may be an indicator of inconsistent performance, either of the equipment or the staff. When these instances occur the CDMO should be able to provide performance records demonstrating that the problem was recognized and mitigated.
Client data must be kept for extended periods to satisfy regulatory requirements; therefore data integrity and security are essential. Data is reviewed both by analytical scientists and quality assurance specialists to ensure that it was accurately recorded. The CDMO’s IT department has responsibility for data confidentiality and access; software features specific user roles, including “full feature” access for the scientists, “review-only” access for quality analysts, and “approver” access for management. Both client and regulatory auditors will insist on review of data integrity and security SOPs.
Many of the analytical techniques used in drug development have existed for decades and continue to be reliable. The US Pharmacopeia and the EU standards for drug testing continue to reference compendial methods that use older analytical technologies; however, a CDMO must be open to acquiring and developing any new analytic methods and technologies a client may require.
Clients appreciate growth in capacity and sophistication. There is an expectation, for any organization helping to support a potentially marketable drug over the course of its patent life, that it works with the drug’s marketer to maintain state-of-the-art analysis techniques. Clients should expect that the CDMO is not only effective in performing the analytical tests the client needs but that they are also getting better and more efficient at those techniques from year to year.